J Clin Lipidol. 2026 Aug 22:S1933-2874(26)00482-4. doi: 10.1016/j.jacl.2026.08.007. Online ahead of print.
ABSTRACT
Familial dysbetalipoproteinemia (FD) is a rare autosomal recessive inherited dyslipidemia caused by homozygous variants of the ε2 allele in the apolipoprotein E (APOE) gene. Phenotypically, it presents as elevated remnant cholesterol and, in some cases, tuberoeruptive xanthomas - a dermatological manifestation. However, the variable penetrance of ε2ε2-mediated FD complicates early recognition. Patients with FD have a markedly increased risk of premature cardiovascular disease (CVD), making early awareness essential to reduce cardiovascular risk. In this case report, we present an otherwise healthy male aged 38 years with a long history of undiagnosed tuberoeruptive xanthomas despite dermatological assessment. Blood lipids had never been evaluated until the patient presented with concomitant symptomatic triple vessel coronary artery disease. Further genotyping showed the patient was homozygous for APOE (NM_000041.4):c.526C>T p.(Arg176Cys). Early preventive intervention is crucial to reduce the risk of premature CVD in high-risk patients, yet the intervention may be delayed for years because of unawareness of subtle clinical signs of dyslipidemia. The diagnosis of tuberoeruptive xanthomas is an important but rare differential diagnosis to dermatological manifestations. The diagnosis requires specific attention because of its association with FD and the high risk of premature CVD. We recommend screening blood lipids during dermatological investigation. FD associated with the homozygous ε2ε2-genotype shows variable penetrance, and secondary factors may complicate the suspicion of an inherited dyslipidemia.
PMID:42705995 | DOI:10.1016/j.jacl.2026.08.007